9-113323143-G-A

Variant names:

• chr9-113323143-G-A
• rs10817479
• NM_001012361.4:c.337C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012361.4(WDR31):​c.337C>T​(p.Pro113Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,613,630 control chromosomes in the GnomAD database, including 3,677 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (287 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3390 hom.)
• Consequence: WDR31 NM_001012361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• Publications: 20 publications found

Genes affected

WDR31 (HGNC:21421): (WD repeat domain 31) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001717329).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR31	NM_001012361.4	MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 6 of 11	NP_001012361.1
	WDR31	NM_145241.5		c.334C>T	p.Pro112Ser	missense	Exon 6 of 11	NP_660284.1
	WDR31	NR_134677.2		n.506C>T		non_coding_transcript_exon	Exon 6 of 11

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR31	ENST00000374193.9	TSL:1 MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 6 of 11	ENSP00000363308.3
	WDR31	ENST00000461942.5	TSL:1	n.487C>T		non_coding_transcript_exon	Exon 6 of 11
	WDR31	ENST00000341761.8	TSL:5	c.334C>T	p.Pro112Ser	missense	Exon 6 of 11	ENSP00000345027.3

Frequencies

GnomAD3 genomes AF: 0.0523 AC: 7962 AN: 152134 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0677

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0680

GnomAD2 exomes AF: 0.0676 AC: 16933 AN: 250538 AF XY: 0.0659

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.0992

Gnomad ASJ exome AF: 0.0482

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.0610

Gnomad NFE exome AF: 0.0617

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0649 AC: 94838 AN: 1461378 Hom.: 3390 Cov.: 31 AF XY: 0.0645 AC XY: 46901 AN XY: 726976

African (AFR) AF: 0.0102 AC: 343 AN: 33470

American (AMR) AF: 0.0949 AC: 4237 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.0489 AC: 1277 AN: 26102

East Asian (EAS) AF: 0.151 AC: 6011 AN: 39696

South Asian (SAS) AF: 0.0570 AC: 4907 AN: 86136

European-Finnish (FIN) AF: 0.0597 AC: 3191 AN: 53406

Middle Eastern (MID) AF: 0.0688 AC: 397 AN: 5768

European-Non Finnish (NFE) AF: 0.0634 AC: 70496 AN: 1111784

Other (OTH) AF: 0.0659 AC: 3979 AN: 60370

GnomAD4 genome AF: 0.0523 AC: 7957 AN: 152252 Hom.: 287 Cov.: 32 AF XY: 0.0527 AC XY: 3926 AN XY: 74454

African (AFR) AF: 0.0126 AC: 525 AN: 41548

American (AMR) AF: 0.0675 AC: 1033 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3468

East Asian (EAS) AF: 0.143 AC: 739 AN: 5176

South Asian (SAS) AF: 0.0569 AC: 274 AN: 4816

European-Finnish (FIN) AF: 0.0605 AC: 643 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4343 AN: 68012

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0607 Hom.: 1143

Bravo AF: 0.0521

TwinsUK AF: 0.0677 AC: 251

ALSPAC AF: 0.0734 AC: 283

ESP6500AA AF: 0.0161 AC: 71

ESP6500EA AF: 0.0665 AC: 572

ExAC AF: 0.0648 AC: 7872

Asia WGS AF: 0.0830 AC: 292 AN: 3478

EpiCase AF: 0.0632

EpiControl AF: 0.0623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.36
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.93
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.068
Sift	Benign	0.43	T
Sift4G	Benign	0.41	T
Polyphen		0.017	B
Vest4		0.035
MPC		0.11
ClinPred		0.0016	T
GERP RS		1.8
Varity_R		0.057
gMVP		0.19
Mutation Taster		=295/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10817479; hg19: chr9-116085423; COSMIC: COSV107448903;